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Title: Atherosclerosis
Description: What is atherosclerosis, its mechanism, its treatment, its furture targeted and possible treatments
Description: What is atherosclerosis, its mechanism, its treatment, its furture targeted and possible treatments
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ATHEROSCLEROSIS
-‐ progressive disease of ARTERIES,
accumulation of LIPIDS and FIBROUS
TISSUE in tunica intima of vessels
-‐ primary cause of CORONARY HEART
DISEASE and STROKE
-‐ leads to MYOCARDIAL ISCHAEMIA
1
...
-‐ Foam cells accumulate, apoptosis explode
and leave lipid core
-‐ Proliferation & matrix formation by intimal
“synthetic” smooth muscle cells forms
fibrous cap
-‐ Thrombosis caused by rupture of fibrous
cap (eg by proteolytic enzymes released by
inflammatory cells)
2
...
2-‐0
...
5% -‐ 2
...
(no more back to
liver to aid in bile acid synthesis) More
cholesterol is needed for bile acid synthesis -‐>
increases hepatic LDL receptor expression -‐>
reduce serum LDL
-‐ ADVERSE : GI intolerance, intefers with other
drug actions eg binds other –ve charged drugs,
impeding their adsorption
FIBRIC ACID DERIVATIVES
-‐ gemfibrozil, fenofibrate
-‐ increases HDL & reduces LDL + VLDL by
activating PPAR-‐alpha which regulates
expression of key protein in HDL synthesis,
HDL mediated reverse cholesterol transport
and lipoprotein lipolysis
-‐ ADVERSE – GI upset, gallstones
NICOTINIC ACID
-‐ niacin
-‐ activate GPCR G protein -‐> inhibits lipolysis
-‐> reduced plasma free fatty acids -‐
>reduced hepatic production of VLDL which
are precursors of LDL -‐> lower serum LDL
levels
-‐ increases HDL by inducing apo – A1
-‐ ADVERSE : flush, itch, headache,
hyperglycaemia, decreased insulin
sensitivity
Ezetimibe
-‐ Indirect inhibition of NPC1L1 -‐> blocks
intestinal cholesterol absorbtion
-‐ Loweres serum LDL levels
-‐ ADVERSE : GI intolerance, joint/back pain
3
Title: Atherosclerosis
Description: What is atherosclerosis, its mechanism, its treatment, its furture targeted and possible treatments
Description: What is atherosclerosis, its mechanism, its treatment, its furture targeted and possible treatments